This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: Inhibition of osteoclast and/or osteoblast activation may down-modulate pathophysiological responses to vaso-occlusion and diminish pain and pain symptoms in Sickle Cell Disease (SCD) Specific Aims: In patients with SCD receiving either 1 or 2 doses of zoledronic acid (ZA): " Evaluate the safety and toxicity of ZA with attention to dental health (specifically, ONJ), renal function, red blood and reticulocyte count, liver health and serum electrolytes " Observe, and to the extent feasible compare between dosing regimens, changes in markers of bone metabolism CTX, bone specific alkaline phosphatase (BSAP), markers of inflammation and pain.